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Izifundo ezahlukeneyo zangaphambi kweklinikhi ze-stent ye-Eustachian tube (ET) ephuhlisiweyo ziyaqhubeka okwangoku, kodwa ayikasetyenziswa kwizenzo zonyango. Kwizifundo zangaphambi kweklinikhi, ii-scaffolds ze-ET zinqunyelwe ekukhuleni kwezicubu ezibangelwa yi-scaffold. Ukusebenza kwe-stent ye-cobalt-chromium sirolimus-eluting (SES) ekuthinteleni ukwanda kwezicubu ezibangelwa yi-stent emva kokubekwa kwe-stent kufundwe kwimodeli ye-ET yeengulube. Iingulube ezintandathu zahlulwe zangamaqela amabini (oko kukuthi iqela lolawulo kunye neqela le-SES) kunye neengulube ezintathu kwiqela ngalinye. Iqela lolawulo lifumene i-stent ye-cobalt-chromium engagqunywanga (n = 6), kwaye iqela le-SES lifumene i-stent ye-cobalt-chromium ene-sirolimus-eluting coating (n = 6). Onke amaqela abulawa emva kweeveki ezi-4 zokubekwa kwe-stent. Ukubekwa kwe-stent kube yimpumelelo kuzo zonke ii-ET ngaphandle kweengxaki ezinxulumene notyando. Akukho nanye kwezi stent eyayinokugcina imo yayo yokuqala ejikelezileyo, kwaye ukuqokelelwa kwe-mucus kwabonwa ngaphakathi nangaphandle kwe-stent kumaqela omabini. Uhlalutyo lwe-Histological lubonise ukuba indawo yokwanda kwezicubu kunye nobukhulu be-submucosal fibrosis kwiqela le-SES yayiphantsi kakhulu kunakwiqela lolawulo. I-SES ibonakala isebenza kakuhle ekuthinteleni ukwanda kwezicubu ezibangelwa yi-scaffold kwiihagu ze-ET. Nangona kunjalo, kufuneka uphando olongezelelweyo ukuqinisekisa izixhobo ezifanelekileyo ze-stents kunye namayeza okuthintela ukwanda.
I-Eustachian tube (ET) inemisebenzi ebalulekileyo kwindlebe ephakathi (umz., ukuphefumla, ukuthintela ukudluliselwa kwezifo kunye nokukhupha okuphumayo kwi-nasopharynx)1. Ikwabandakanya ukukhuselwa kwizandi ze-nasopharyngeal kunye nokubuyela kwesisu2. I-ET idla ngokuvalwa, kodwa ivuleka ngokuginya, ukukhafula, okanye ukuhlafuna. Nangona kunjalo, ukungasebenzi kakuhle kwe-ET kunokwenzeka ukuba i-tube ayivuli okanye ayivali kakuhle3,4. Ukungasebenzi kakuhle kwe-ET okukhukulisayo (okuthinteleyo) kuyayithomalalisa imisebenzi ye-ET kwaye, ukuba le misebenzi ayigcinwanga, inokuphuhla ibe yi-acute okanye i-chronic otitis media, esinye sezifo eziqhelekileyo kwi-ENT practice. Unyango lwangoku lokungasebenzi kakuhle kwe-ET (umz., utyando lwempumlo, ukufakwa kwe-ventilation tube, kunye namayeza) lusetyenziswa kwizigulana. Nangona kunjalo, olu nyango lunemisebenzi emincinci kwaye lunokukhokelela ekuthintelweni kwe-ET, usulelo, kunye nokugqobhoka kwe-tympanic membrane okungaguqukiyo3,6,7. I-Eustachian tube balloon angioplasty iye yaziswa njengonyango olulolunye lokungasebenzi kakuhle kwe-ET 8. Nangona izifundo ezininzi ukusukela ngo-2010 zibonise ukuba ukulungiswa kwebhaluni yetyhubhu ye-Eustachian kungcono kunonyango oluqhelekileyo lokungasebenzi kakuhle kwe-ET, ezinye izigulana aziphenduli ekukhuleni kwe-8,9,10,11. Ngoko ke, ukutshiza i-stenting kunokuba lukhetho olusebenzayo lonyango12,13. Nangona izifundo ezininzi eziqhubekayo zangaphambi kweklinikhi zivavanya ukwenzeka kobuchwephesha kunye nokuphendula kwezicubu emva kokubekwa kwe-stent kwi-ET, i-stent-induced tissue hyperplasia ngenxa yomonakalo woomatshini isalokhu iyingxaki ebalulekileyo emva kotyando14,15,16,17,18,19. I-drug-coated, egcwele ii-anti-proliferative agents iyayiphucula le meko.
Ii-stent ezisebenzisa amayeza ziye zasetyenziswa ukuthintela i-in-stent restenosis ebangelwa yi-tissue kunye ne-neointimal hyperplasia emva kokubekwa kwe-stent. Ngokwesiqhelo, ii-stent scaffolds okanye ii-linings zigqunywe ngamayeza (umz., i-everolimus, i-paclitaxel, kunye ne-sirolimus)20,23,24. I-Sirolimus liyeza eliqhelekileyo elithintela ukwanda kwamanqanaba e-restenosis cascade (umz., ukudumba, i-neointimal hyperplasia, kunye nokwenziwa kwe-collagen)25. Ke ngoko, olu phononongo lucinge ukuba ii-stent ezigqunywe yi-sirolimus zinokuthintela i-stent-induced tissue hyperplasia kwiihagu ze-ET (Umfanekiso 1). Injongo yolu phononongo yayikukuphanda ukusebenza kakuhle kwe-sirolimus-eluting stents (SES) ekuthinteleni ukwanda kwezicubu ezigqunywe yi-stent emva kokubekwa kwe-stent kwimodeli ye-porcine ET.
Umfanekiso ocacileyo we-stent ye-cobalt-chromium sirolimus-eluting (SES) yokunyanga ukungasebenzi kakuhle kwetyhubhu ye-Eustachian, ebonisa ukuba i-stent ye-sirolimus-eluting ithintela ukwanda kwezicubu ezibangelwa yi-stent.
Iistenti ze-alloy zeCobalt-chromium (Co-Cr) zenziwe ngeetyhubhu ze-alloy zeCo-Cr ezisikiweyo nge-laser (Genoss Co., Ltd., Suwon, Korea). Iqonga le-stent lisebenzisa i-open double bond enoyilo oludibeneyo ukuze kube lula ukuguquguquka ngamandla e-radial afanelekileyo, ukufinyeza kunye nokuhambelana. I-stent yayinobubanzi be-3 mm, ubude be-18 mm, kunye nobukhulu be-strut obuyi-78 µm (Umzobo 2a). Ubukhulu besakhelo se-alloy yeCo-Cr bumiselwe ngokusekelwe kuphando lwethu lwangaphambili.
I-Cobalt-chromium (Co-Cr) alloy stent kunye ne-metal guide sheath yokubeka i-Eustachian tube stent. Iifoto zibonisa (a) i-Co-Cr alloy stent kunye (b) ne-balloon catheter ene-stent-clamped. (c) I-balloon catheter kunye ne-stent zifakwe ngokupheleleyo. (d) I-metal guide sheath yenzelwe imodeli ye-porcine Eustachian tube.
I-Sirolimus yafakwa kumphezulu we-stent kusetyenziswa ubuchwepheshe be-ultrasonic spray. I-SES yenzelwe ukukhupha phantse i-70% yomthwalo wokuqala weyeza (1.15 µg/mm2) kwiintsuku zokuqala ezingama-30 emva kokufakwa. Ingubo encinci kakhulu ye-3 µm ifakwa kuphela kwicala elikufutshane le-stent ukuze kufezekiswe iprofayili yokukhululwa kweyeza efunekayo kwaye kuncitshiswe ubungakanani be-polymer; le ngubo inokubola iqulethe i-copolymer ye-lactic kunye ne-glycolic acids kunye nomxube okhethekileyo we-poly(1)-lactic acid)26,27. Ii-Co-Cr alloy stents zafakwa kwii-catheters zebhaluni ezinobubanzi obuyi-3 mm kunye nobude obuyi-28 mm (Genoss Co., Ltd.; Umfanekiso 2b). Ezi stents ziyafumaneka eMzantsi Korea kunyango lwesifo sentliziyo sentliziyo.
Iqokobhe lesinyithi elisandul’ ukuphuhliswa lemodeli ye-ET yehagu lenziwe ngentsimbi engagqwaliyo (Umzobo 2c). Ububanzi bangaphakathi nobangaphandle beqokobhe buyi-2 mm kunye ne-2.5 mm, ngokulandelelana, ubude bubonke buyi-250 mm. I-distal sheath engama-30 mm yayigobile ibe yi-J-shape kwi-engile ye-15° ukuya kwi-axis ukuvumela ukufikelela okulula ukusuka empumlweni ukuya kwi-nasopharyngeal orifice ye-ET kwimodeli yehagu.
Olu phononongo luvunyiwe yiKomiti yoLondolozo lweZilwanyana kunye nokusetyenziswa kweZiko le-Asan Institute of Life Sciences (eSeoul, eMzantsi Korea) kwaye luhambelana neMigaqo yeSizwe yeZiko lezeMpilo yoNyango lweZilwanyana zeLebhu (IACUC-2020-12-189). . Olu phononongo lwenziwe ngokuhambelana nezikhokelo ze-ARRIVE. Olu phononongo lusebenzise ii-ET ezili-12 kwiihagu ezi-6 ezinobunzima obuyi-33.8-36.4 kg kwiinyanga ezi-3 ubudala. Iihagu ezintandathu zahlulwe zaba ngamaqela amabini (oko kukuthi iqela lolawulo kunye neqela le-SES) kunye neehagu ezintathu kwiqela ngalinye. Iqela lolawulo lifumene i-stent ye-Co-Cr alloy engagqunywanga, ngelixa iqela le-SES lifumene i-stent ye-Co-Cr alloy eluting sirolimus. Zonke iihagu zazinokufikelela simahla emanzini nasekutyeni kwaye zigcinwe kuma-24°C ± 2°C kumjikelo weeyure ezili-12 zasemini nasebusuku. Emva koko, zonke iihagu zanikelwa emva kweeveki ezi-4 emva kokubekwa kwe-stent.
Zonke iihagu zifumene umxube we-50mg/kg ye-zolazepam, i-50mg/kg ye-teletamide (i-Zoletil 50; i-Virbac, i-Carros, i-France) kunye ne-10mg/kg ye-xylazine (i-Rompun; i-Bayer HealthCare, i-Les Varkouzins, i-Germany). Emva koko ityhubhu ye-tracheal yafakwa ngokuphefumla i-0.5-2% ye-isoflurane (i-Ifran®; i-Hana Pharm. Co., i-Seoul, i-Korea) kunye ne-oxygen 1:1 (510 ml/kg/min) ukuze kuthomalaliswe i-anesthesia. Iihagu zabekwa kwindawo yokulala phantsi kwaye kwenziwa i-baseline endoscopy (i-VISERA 4K UHD rhinolaryngoscope; i-Olympus, i-Tokyo, i-Japan) ukuze kuhlolwe i-nasopharyngeal orifice ye-ET. I-metal guide sheath yadluliselwa empumlweni ukuya kwi-nasopharyngeal orifice ye-ET phantsi kolawulo lwe-endoscopic (Umzobo 3a, b). I-catheter yebhaluni, i-corrugated stent, ifakwa nge-introser kwi-ET de incam yayo idibane nokumelana kwi-osteochondral isthmus ye-ET (Umzobo 3c). I-catheter yebhaluni yafunxwa ngokupheleleyo nge-saline kwi-atmospheres ezili-9, njengoko kumiselwe yi-manometer monitor (Umzobo 3d). I-catheter yebhaluni yasuswa emva kokubekwa kwe-stent (Umzobo 3f), kwaye ukuvulwa kwe-nasopharyngeal kwavavanywa ngononophelo i-endoscopy ukuze kujongwe iingxaki zotyando (Umzobo 3f). Zonke iihagu zaye zavavanywa nge-endoscopy ngaphambi nasemva kokufakwa kwe-stent, kunye neeveki ezi-4 emva kokufakwa kwe-stent, ukuze kuvavanywe i-patency yendawo ye-stent kunye nokukhupha okujikelezileyo.
Amanyathelo obuchwephesha okubeka i-stent kwityhubhu ye-eustachian (ET) yehagu phantsi kolawulo lwe-endoscopic. (a) Umfanekiso we-Endoscopic obonisa ukuvulwa kwe-nasopharyngeal (utolo) kunye ne-metal guide sheath (utolo) efakiweyo. (b) Ukufakwa kwe-metal sheath (utolo) kwi-nasopharyngeal open. (c) I-balloon catheter (utolo) ene-stent-clamped ingeniswa kwi-ET nge-sheath (utolo). (d) I-balloon catheter (utolo) ivuthelwe ngokupheleleyo. (e) Isiphelo esikufutshane se-stent siphuma kwi-ET orifice ye-nasopharynx. (f) Umfanekiso we-Endoscopic obonisa i-stent lumen patency.
Zonke iihagu zibulawe ngokunikwa i-75 mg/kg ye-potassium chloride ngenaliti yemithambo yendlebe. Amacandelo e-median sagittal entloko yehagu enziwe kusetyenziswa i-chainsaw elandelwa kukukhutshwa ngononophelo kweesampuli zezicubu ze-ET scaffold ukuze kuhlolwe i-histological (Umzobo Ongezelelweyo 1a,b). Iisampuli zezicubu ze-ET zilungisiwe kwi-10% ye-neutral buffered formalin kangangeeyure ezingama-24.
Iisampulu zezicubu ze-ET zaye zasuswa ngokulandelelana nge-alcohol yoxinzelelo olwahlukeneyo. Iisampulu zafakwa kwiibhloko ze-resin ngokungena nge-ethylene glycol methacrylate (Technovit 7200® VLC; Heraus Kulzer GMBH, Wertheim, Germany). Amacandelo e-Axial enziwe kwiisampuli zezicubu ze-ET ezifakwe kwiindawo ezikufutshane nezikude (Umfanekiso oNcedisayo 1c). Iibhloko ze-polymer emva koko zafakelwa kwiislayidi zeglasi ze-acrylic. Iislayidi ze-resin block zaye zapholishwa ngephepha le-silicon carbide lobukhulu obahlukeneyo ukuya kuthi ga kubukhulu be-20 µm kusetyenziswa inkqubo yegridi (Apparatebau GMBH, Hamburg, Germany). Zonke iislayidi zahlolwa nge-histological nge-hematoxylin kunye ne-eosin staining.
Uvavanyo lwe-histological lwenziwe ukuvavanya ipesenti yokwanda kwezicubu, ubukhulu be-submucosal fibrosis, kunye nobungakanani bokungena kweeseli ezivuthayo. Ipesenti ye-tissue hyperplasia enendawo encinci ye-ET cross-sectional ibalwe ngokusombulula i-equation:
Ubukhulu be-submucosal fibrosis bulinganiswe ngokuthe nkqo ukusuka kwi-stent struts ukuya kwi-submucosa. Ubungakanani bokungena kweeseli ezivuthayo bujongwa ngokwahlukileyo ngokusasazwa kunye nobuninzi beeseli ezivuthayo, ezizezi: idigri yoku-1 (encinci) - ukungena kwe-leukocyte enye; idigri yesi-2 (encinci ukuya kwephakathi) - ukungena kwe-leukocyte egxile kwi-focal; idigri yesi-3 (ephakathi) - idityaniswe. kunye nee-leukocytes ezingakwaziyo ukwahlula phakathi kwendawo nganye; ii-leukocytes zebanga lesi-4 (eziphakathi ukuya kwezikhulu) ezingena kwi-submucosa yonke, kunye ne-diffuse yebanga lesi-5 (enzima) ebandakanya i-necrosis eninzi. Ubukhulu be-submucosal fibrosis kunye nedigri yokungena kweeseli ezivuthayo bufunyenwe ngomyinge wamanqaku asibhozo ajikeleze umjikelezo. Uhlalutyo lwe-histological lwe-ET lwenziwe kusetyenziswa i-microscope (BX51; Olympus, Tokyo, Japan). Ukulinganiswa kufunyenwe kusetyenziswa isoftware yeCaseViewer (CaseViewer; 3D HISTECH Ltd., Budapest, Hungary). Uhlalutyo lwedatha ye-histological lusekelwe kwisivumelwano sababukeli abathathu abangazange bathathe inxaxheba kolu phando.
Uvavanyo lweMann-Whitney U lusetyenziselwe ukuhlalutya umahluko phakathi kwamaqela njengoko kufuneka. I-p < 0.05 ithathwe njengebalulekileyo ngokwezibalo. I-p < 0.05 ithathwe njengebalulekileyo ngokwezibalo. Значение p < 0,05 считалось статистически значимым. Ixabiso le-p < 0.05 lithathwe njengelibalulekileyo ngokwezibalo. p <0.05 被认为具有统计学意义. p < 0.05 p <0,05 считали статистически значимым. p <0.05 ithathwe njengebalulekileyo ngokwezibalo. Uvavanyo lwe-Mann-Whitney U olulungisiweyo yiBonferroni lwenziwe kwi-p values ​​< 0.05 ukuze kufunyanwe umahluko kwiqela (p < 0.008 njengebalulekileyo ngokwezibalo). Uvavanyo lwe-Mann-Whitney U olulungisiweyo yiBonferroni lwenziwe kwi-p values ​​​​< 0.05 ukuze kufunyanwe umahluko kwiqela (p < 0.008 njengebalulekileyo ngokwezibalo). U-критерий Манна-Уитни с поправкой на Бонферрони был выполнен для значений p <0,05 для выявления групповых различи00 (p08, 1996, p. значимое). Uvavanyo lweMann-Whitney U oluhlengahlengiswe yiBonferroni lwenziwe kwixabiso le-p <0.05 ukuze kufunyanwe umahluko kwiqela (p <0.008 njengobalulekileyo ngokwezibalo).对p 棄umfanekiso weskrini < 0.05 进行Bonferroni 校正的Mann-Whitney U U-критерий Манна-Уитни с поправкой на Бонферрони был выполнен для значений p < 0,05 для выявления групповых различы0,0 11 значимым). Uvavanyo lwe-Mann-Whitney U oluhlengahlengiswe yiBonferroni lwenziwe kwi-p < 0.05 ukuze kufunyanwe umahluko kwiqela (p < 0.008 yayibalulekile ngokwezibalo).Uhlalutyo lwezibalo lwenziwe kusetyenziswa isoftware ye-SPSS (inguqulelo 27.0; SPSS, IBM, Chicago, IL, USA).
Zonke iindawo zokubeka i-stent yeengulube ziphumelele ngobuchwephesha. I-sheath yesikhokelo sesinyithi ifakwe ngempumelelo kwi-nasopharyngeal orifice ye-ET phantsi kolawulo lwe-endoscopic, nangona ukwenzakala kwe-mucosal kunye nokopha okubonakalayo kwabonwa kwiisampuli ezi-4 kwezili-12 (33.3%) ngexesha lokufakwa kwe-sheath yesinyithi. Emva kweeveki ezi-4, ukopha okubonakalayo kwayeka ngokuzenzekelayo. Zonke iihagu zasinda de kwaphela uphando ngaphandle kweengxaki ezinxulumene ne-stent.
Iziphumo ze-Endoscopy ziboniswe kuMfanekiso 4. Ngexesha lokulandelelana kweeveki ezi-4, ii-stents zahlala zikho kuzo zonke iihagu. Ukuqokelelwa kwe-mucus ngaphakathi nangaphandle kwe-stent ye-ET kwabonwa kuzo zonke ii-ET (100%) kwiqela lolawulo kunye nee-ET ezintathu (50%) kwezintandathu kwiqela le-SES, kwaye akukho mahluko kwiziganeko phakathi kwamaqela amabini (p = 0.182). Akukho nanye kwezi stents ezifakiweyo eyayinokugcina imo engqukuva.
Imifanekiso ye-Endoscopic yetyhubhu ye-Eustachian (ET) yehagu kwiqela lolawulo kunye neqela eline-cobalt-chromium stent (CXS) ekhupha i-sirolimus. (a) Umfanekiso wesiseko we-endoscopic othathwe ngaphambi kokubekwa kwe-stent obonisa ukuvulwa kwe-nasopharyngeal (utolo) lwe-ET. (b) Umfanekiso we-Endoscopic othathwe kwangoko emva kokubekwa kwe-stent obonisa i-ET yokubekwa kwe-stent. Ukopha okudibeneyo kuye kwabonwa ngenxa ye-metal guide sheath (utolo). (c) Umfanekiso we-Endoscopic othathwe kwiiveki ezi-4 emva kokubekwa kwe-stent ubonisa ukuqokelelwa kwe-mucus ejikeleze i-stent (utolo). (d) Umfanekiso we-Endoscopic obonisa ukuba i-stent ayinakuhlala ijikelezile (utolo).
Iziphumo ze-histological ziboniswe kuMfanekiso 5 kunye noMfanekiso oNgezelelayo 2. Ukwanda kwezicubu kunye nokwanda kwe-submucosal fibrous phakathi kwezithuba ze-stent kwi-ET lumen yamaqela omabini. Ipesenti ephakathi yendawo ye-tissue hyperplasia yayinkulu kakhulu kwiqela lolawulo kunakwiqela le-SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p < 0.001). Ipesenti ephakathi yendawo ye-tissue hyperplasia yayinkulu kakhulu kwiqela lolawulo kunakwiqela le-SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p < 0.001). Средний процент площади гиперплазии тканей был значительно больше в контрольной группе, чем в группе СЭС (79,68% 48,36% ± 10,06%, p <0,001). Ipesenti ephakathi yendawo ye-tissue hyperplasia yayinkulu kakhulu kwiqela lolawulo kunakwiqela le-SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p < 0.001).I-SES 组 (79.48% ± 6.82% vs.48.36% ± 10.06%，p < 0.001）。 48.36% ± 10.06%，p < 0.001）。 Средний процент площади гиперплазии тканей в контрольной группе был значительно выше, чем в группе СЭС (79,6,48,6%2% ± 10,06%, p <0,001). Ipesenti ephakathi yendawo ye-tissue hyperplasia kwiqela lolawulo yayiphezulu kakhulu kunakwiqela le-SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p < 0.001). Ngaphezu koko, ubukhulu obuphakathi be-submucosal fibrosis nabo babuphezulu kakhulu kwiqela lolawulo kunakwiqela le-SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p < 0.001). Ngaphezu koko, ubukhulu obuphakathi be-submucosal fibrosis nabo babuphezulu kakhulu kwiqela lolawulo kunakwiqela le-SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p < 0.001). Более того, средняя толщина подслизистого фиброза также была значительно выше в контрольной группе, чем в группе, 425, ± 50,50 ± 0,20 мм, p <0,001). Ngaphezu koko, ubukhulu obuphakathi be-submucosal fibrosis nabo babuphezulu kakhulu kwiqela lolawulo kunakwiqela le-SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p < 0.001).I-SES 组（1.41 ± 0.25 vs.0.56 ± 0.20 mm，p < 0.001）。 0.56±0.20mm，p<0.001）。 Кроме того, средняя толщина подслизистого фиброза в контрольной группе также была значительно выше, чем в группе СЭ0 СЭ0, 510, 410, 50,50, 5,5, 6 (1, 5, 5, 5, 5). ± 0,20 мм, p <0,001). Ukongeza, ubukhulu obuphakathi be-submucosal fibrosis kwiqela lolawulo nabo babuphezulu kakhulu kunakwiqela le-SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p < 0.001).Nangona kunjalo, bekungekho mahluko ubalulekileyo kwinqanaba lokungena kweeseli ezivuthayo phakathi kwamaqela amabini (iqela lolawulo [3.50 ± 0.55] xa kuthelekiswa neqela le-SES [3.00 ± 0.89], p = 0.270).
Uhlalutyo lovavanyo lwe-histological lwamaqela amabini ee-stents abekwe kwi-Eustachian lumen. (a, b) Indawo ye-tissue hyperplasia (1 ye-a kunye ne-b) kunye nobukhulu be-submucosal fibrosis (2 ye-a kunye ne-b; iintolo eziphindwe kabini) zazinkulu kakhulu kwiqela lolawulo kunakwiqela le-SES eline-strut stenting (amachaphaza amnyama), indawo ye-lumen emxinwa (etyheli) kunye nendawo ye-stent yokuqala (ebomvu). Ubungakanani bokungena kweeseli ezivuthayo (3 ze-a kunye ne-b; iintolo) abuzange buhluke kakhulu phakathi kwamaqela amabini. (c) Iziphumo ze-histological zepesenti yendawo ye-tissue hyperplasia, (d) ubukhulu be-submucosal fibrosis, kunye (e) nobungakanani bokungena kweeseli ezivuthayo kwiiveki ezi-4 emva kokubekwa kwe-stent kuwo omabini amaqela. I-SES, i-cobalt-chromium sirolimus eluting stent.
Ii-stent ezisusa amayeza zinceda ukuphucula i-stent patency kwaye zithintele i-stent restenosis20,21,22,23,24. Ii-strictures ezibangelwa yi-stent zivela ekubunjweni kwezicubu ze-granulation kunye notshintsho lwezicubu ze-fibrous kwizitho ezahlukeneyo ezingezizo zemithambo yegazi, kubandakanya i-esophagus, i-trachea, i-gastroduodenum, kunye ne-bile ducts. Amayeza anjenge-dexamethasone, i-paclitaxel, i-gemcitabine, i-EW-7197, kunye ne-sirolimus asetyenziswa kumphezulu we-wire mesh okanye i-stent coating ukuthintela okanye ukunyanga i-tissue hyperplasia emva kokufakwa kwe-stent29,30,34,35,36. Izinto ezintsha zamva nje kwicandelo le-stents ezininzi ezisebenzisa itekhnoloji ye-fusion ziyaphandwa ngokukhutheleyo kunyango lwezifo ezingezizo zemithambo yegazi37,38,39. Kwisifundo sangaphambili kwimodeli ye-porcine ET, ukwanda kwezicubu ezibangelwa yi-scaffold kwabonwa. Nangona uphuhliso lwe-stent kwi-ET lungaqondwa kakuhle, impendulo yezicubu emva kokubekwa kwe-stent ifunyenwe ifana neyezinye izitho zelanga ezingezizo imithambo yegazi19. Kolu phononongo lwangoku, i-SES isetyenziselwe ukuthintela ukwanda kwezicubu ezibangelwa yi-scaffold kwimodeli ye-ET yeengulube. I-Sirolimus inetyhefu kwii-islets ze-pancreatic kunye nemigca yeeseli ze-beta, inciphisa ukusebenza kweseli kwaye iphucula i-apoptosis40,41. Esi siphumo sinokunceda ukuthintela ukwakheka kokwanda kwezicubu ngokuvuselela ukufa kweseli. Uphononongo lwethu lubonise ukuba ukusetyenziswa kokuqala kwe-stents ezibangela iziyobisi kwi-ET kuthintele ngempumelelo ukwanda kwezicubu ezibangelwa yi-stent kwi-ET.
I-stent ye-Co-Cr alloy enwebekayo esetyenziswa kolu phononongo ifumaneka lula njengoko isetyenziswa kakhulu ukunyanga isifo semithambo yentliziyo 42. Ukongeza, ii-alloys ze-Co-Cr zineempawu zoomatshini (umzekelo, amandla aphezulu e-radial kunye namandla angaguqukiyo) 43. Ngokwe-endoscopy yolu phononongo lwangoku, i-stent ye-Co-Cr alloy esetyenziselwa i-ET yeehagu ayinakugcina imo engqukuva kuzo zonke iihagu ngenxa yokungomelelanga ngokwaneleyo kwaye ayinakho ukuzikhulisa. Imo ye-stent efakiweyo inokutshintshwa nangokuhambahamba kwi-ET yesilwanyana esiphilayo (umzekelo, ukuhlafuna nokuginya). Iimpawu zoomatshini ze-Co-Cr alloy stents ziye zaba yingxaki ekubekweni kwee-stent ze-porcine ET. Ukongeza, ukubekwa kwe-stent kwi-isthmus kunokubangela i-ET evulekileyo ngokusisigxina. I-ET evulekileyo okanye eyandisiweyo rhoqo ivumela intetho kunye nezandi ze-nasopharyngeal, i-gastrointestinal reflux, kunye ne-pathogens1 ukuba zihambe ziye endlebeni ephakathi, nto leyo ebangela ukucaphuka kwe-mucosal kunye nosulelo. Ngoko ke, kufuneka kuphetshwe imingxuma engapheliyo ye-nasopharyngeal. Ngenxa yesakhiwo se-ET cartilage, ii-scaffolds zikhethwa ukuba zenziwe ngee-alloys zememori yesimo ezineempawu ze-superelastic, ezifana ne-nitinol. Ngokubanzi, ukukhupha okukhulu kufunyenwe ngaphakathi nangaphandle kwe-nasopharyngeal orifice ye-stent. Ekubeni intshukumo eqhelekileyo ye-mucus ivaliwe, kulindeleke ukuba imfihlo iqokeleleke kwii-scaffolds eziphuma kwi-nasopharyngeal open. Ukuthintela usulelo lwendlebe ephakathi olunyukayo yenye yeenjongo eziphambili ze-ET, kwaye ukubekwa kwee-stents eziphuma ngaphaya kwe-ET kufuneka kuphetshwe, kuba ukudibana ngqo kwee-stents ne-nasopharyngeal bacteria flora kunokukhokelela ekwandeni kosulelo olunyukayo.
I-Eustachian tube balloon plasty ngokusebenzisa ukuvulwa kwe-nasopharyngeal lunyango olutsha olungena kakhulu kwi-ET dysfunction olujolise ekuvuleni nasekukhuliseni inxalenye ye-cartilaginous ye-ET8,9,10,46. Nangona kunjalo, indlela yokunyanga esisiseko ayikachongwa47 kwaye iziphumo zayo zexesha elide zinokuba ziphantsi kakhulu8,9,11,46. Phantsi kwezi meko, i-metal stenting yexeshana inokuba lukhetho olusebenzayo lonyango kwizigulana ezingaphenduliyo ekulungisweni kwe-Eustachian tube balloon, kwaye ukuba nokwenzeka kwe-ET stenting kubonakaliswe kwizifundo ezininzi zangaphambi kweklinikhi. Ii-scaffolds ze-Poly-l-lactide zafakwa nge-membrane ye-tympanic kwi-chinchillas nakwiimvundla ukuvavanya ukunyamezeleka kunye nokuwohloka kwi-vivo17,18. Ukongeza, imodeli yegusha yenziwe ukuvavanya iprofayili ye-metal balloon expandable stents kwi-vivo. Kwisifundo sethu sangaphambili, imodeli ye-ET yeengulube yaphuhliswa ukuze iphande ukuba kunokwenzeka na ukuvavanya iingxaki ezibangelwa yi-stent,19 nto leyo enika isiseko esiqinileyo solu phononongo ukuze iphande ukusebenza kakuhle kwe-SES kusetyenziswa iindlela ezazimiselwe ngaphambili. Kolu phononongo, i-SES yafunyanwa ngempumelelo kwi-cartilage kwaye yathintela ngempumelelo ukwanda kwezicubu. Akukho ngxaki zinxulumene ne-stent, kodwa bekukho ukwenzakala kwe-mucosal okubangelwe yi-metal guide sheath kunye nokopha okudibeneyo okwaphela ngokuzenzekelayo kwiiveki ezi-4. Ngenxa yeengxaki ezinokubakho ze-metal sheaths, ukuphucula inkqubo yokuhambisa i-SES kungxamisekile kwaye kubalulekile.
Olu phononongo lunemida ethile. Nangona iziphumo ze-histological zahluka kakhulu phakathi kwamaqela, inani lezilwanyana kolu phononongo lalincinci kakhulu ukuba lingahlalutywa ngokwezibalo ezinokuthenjwa. Nangona ababukeli abathathu bengakhange babonwe ukuba bavavanye ukuguquguquka kwababukeli, inqanaba lokungena kweeseli ezivuvukalayo ezingaphantsi komlomo lamiselwa ngokwalo ngokusekelwe ekusasazweni nasekuxinaneni kweeseli ezivuvukalayo ngenxa yobunzima bokubala iiseli ezivuvukalayo. Ekubeni uphando lwethu lwenziwe kusetyenziswa inani elincinci lezilwanyana ezinkulu, kwasetyenziswa idosi enye yeyeza, izifundo ze-pharmacokinetic kwi-vivo azizange zenziwe. Izifundo ezongezelelweyo ziyafuneka ukuqinisekisa idosi efanelekileyo yeyeza kunye nokhuseleko lwe-sirolimus kwi-ET. Okokugqibela, ixesha lokulandelela leeveki ezi-4 nalo lingumda wophando, ngoko ke izifundo malunga nokusebenza kwexesha elide kwe-SES ziyafuneka.
Iziphumo zolu phononongo zibonisa ukuba i-SES inokuthintela ngempumelelo ukwanda kwezicubu ezibangelwa kukwenzakala koomatshini emva kokubekwa kwee-scaffold ze-Co-Cr alloy ezinwebekayo kwimodeli ye-ET yehagu. Kwiiveki ezine emva kokubekwa kwe-stent, izinto eziguquguqukayo ezinxulumene nokwanda kwezicubu ezibangelwa yi-stent (kubandakanya indawo yokwanda kwezicubu kunye nobukhulu be-submucosal fibrosis) zaziphantsi kakhulu kwiqela le-SES kunakwiqela lolawulo. I-SES ibonakala isebenza ekuthinteleni ukwanda kwezicubu ezibangelwa yi-scaffold kwiihagu ze-ET. Nangona uphando olongezelelweyo lufuneka ukuvavanya izixhobo ezifanelekileyo ze-stent kunye nemilinganiselo yamayeza, i-SES inamandla okunyanga asekuhlaleni ekuthinteleni i-ET tissue hyperplasia emva kokubekwa kwe-stent.
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